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Top clinical pharmacology myths busted (Proceedings)

1) Morphine cannot be used in cats due to CNS excitement and slow metabolism AND Morphine causes histamine release in dogs resulting in severe hypotension AND The most common adverse effects of opioids are cardiovascular and respiratory depression

Morphine is often used in cats without severe adverse effects or CNS excitement. "Morphine mania" was produced in cats by administering 5-20 mg/kg SC – a dose 20-100 times the clinically recommended dose. High doses of opioids in any species can produce CNS excitement and seizures. The plasma half-life of morphine in cats is ~1.3 hours compared to ~1 hour in dogs. Morphine is rapidly eliminated in cats, but by a different metabolic pathway (sulfate conjugation) compared to dogs and other species (glucuronide conjugation). The dose used in cats is lower (0.25 mg/kg IV, IM, SC q 2-4 hrs) because the volume of distribution in cats is lower compared to dogs. The lower volume of distribution (Vd) means higher plasma concentrations (Cp) are achieved with a given dose (Dose=Vd*Cp). The dosing interval is the same however since the half-lives are similar.

High doses of any opiate can produce bradycardia, vasodilation and subsequently hypotension. Clinically relevant doses of morphine (0.5 mg/kg IV or less) produce large increases in histamine release (~500 fold increase) but have minimal effects on blood pressure. The myth has been propagated due to high doses of morphine (3 mg/kg IV – 6 times the recommended IV dose) which result in dramatic decreases in MAP (110 mm to 30 mm Hg). The same study administered 0.3 mg/kg morphine IV and saw no significant changes in blood pressure or histamine in dogs. A separate study administered 0.5 mg/kg IV morphine to dogs with no concurrent medication which also resulted in no significant changes in blood pressure. Hypotension can be encountered and exacerbated when morphine is administered concurrently with other drugs which cause vasodilation (acepromazine, isoflurane, sevoflurane, propofol, et al) or result in decreased cardiac output (isoflurane, sevoflurane, propofol, thiopental, pentobarbital, et al).

The most common adverse effects of opioids are hypothermia, bradycardia, sedation, nausea, vomiting, panting, and defecation. Despite the pronounced bradycardia, cardiac output remains stable, due to increased stroke volume in animals administered clinically recommended dosages. A dose-dependent respiratory depression does occur with opioids, but clinically recommended dosages produce clinically insignificant respiratory depressant effects. Mild respiratory depression is a concern in animals with head trauma, some pre-existing pulmonary diseases, or when combined with other respiratory depressants.

2) Ciprofloxacin and enrofloxacin are identical antibiotics and are broad spectrum

Ciprofloxacin and enrofloxacin have significantly different pharmacokinetic properties. Fluoroquinolone efficacy is best related to the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC:MIC) with optimal dosages achieving a ratio of 125 or greater. Resistance to fluoroquinolones is minimized by achieving a maximum plasma concentration (CMAX) to MIC ratio of 8 or greater.

Ciprofloxacin administered 15 mg/kg PO q 12 hours results in an AUC of ~ 24 hr*mcg/mL per day. Therefore this dose would be optimal for bacteria with an MIC of 0.2 mcg/mL or less. The CMAX after 15 mg/kg of ciprofloxacin is ~ 2.0 mcg/mL which would decrease the potential resistance in bacteria with an MIC of 0.25 mcg/mL or less.

Enrofloxacin administered 5 mg/kg PO results in an enrofloxacin AUC of 4.5 hr*mcg/mL and a ciprofloxacin AUC 2.7 hr*mcg/mL for a total of 7.2 hr*mcg/mL sufficient for bacteria with an MIC of 0.06 mcg/mL or less. The CMAX of enrofloxacin is 1.2 mcg/mL and ciprofloxacin is 0.4 mcg/mL for a total of ~1.6 mcg/mL sufficient to delay resistance in bacteria with an MIC of 0.2 mcg/mL or less.